Abstract

Aim

There is a clinical need for biomarkers of response to adjuvant 5-fluorouracil (5-FU) in colon cancer (CC). The current project seeks to validate a predictive 5-FU gene expression profile. A similar model has recently been validated with MD Anderson in three different clinical settings [1] and with researchers from AstraZeneca with fulvestrant [2].

Methods

The 5-FU profile consisted of in total 205 positively and negatively correlated genes mapped to 669 probe sets (on the ALMAC Colon DSA). This profile was tested using expression data obtained from a Colon DSA gene expression array from ALMAC applied on the PETACC-3 CC population [3] with formalin fixed paraffin embedded (FFPE) tissue from 636 stage III CC patients treated adjuvantly with 5-FU with or without irinotecan. It was also tested on ALMAC Colon DSA data obtained from FFPE tissue from 359 stage II CC patients who did not receive adjuvant treatment [4]. The analyses were performed using Cox proportional hazards (CPH) regression models and Kaplan-Meier curves. The logrank test was used to compare the survival distributions.